rs2718107

Variant names:

• chr7-129198818-C-A
• rs2718107
• NM_005631.5:c.332-4566C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-129198818-C-A
• chr7-129198818-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005631.5(SMO):​c.332-4566C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,046 control chromosomes in the GnomAD database, including 18,217 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (18217 hom., cov: 32)
• Consequence: SMO NM_005631.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414
• Publications: 7 publications found

Genes affected

SMO (HGNC:11119): (smoothened, frizzled class receptor) The protein encoded by this gene is a G protein-coupled receptor that interacts with the patched protein, a receptor for hedgehog proteins. The encoded protein tranduces signals to other proteins after activation by a hedgehog protein/patched protein complex. [provided by RefSeq, Jul 2010]

SMO Gene-Disease associations (from GenCC):

• Curry-Jones syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P
• congenital hypothalamic hamartoma syndrome

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, ClinGen
• Hirschsprung disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• medulloblastoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMO	NM_005631.5	c.332-4566C>A		intron_variant	Intron 1 of 11	ENST00000249373.8	NP_005622.1
SMO	XM_047420759.1	c.-173-3805C>A		intron_variant	Intron 1 of 12		XP_047276715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMO	ENST00000249373.8	c.332-4566C>A		intron_variant	Intron 1 of 11	1	NM_005631.5	ENSP00000249373.3
SMO	ENST00000655644.1	n.*196-4566C>A		intron_variant	Intron 2 of 11			ENSP00000499377.1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73203 AN: 151928 Hom.: 18205 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.528

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.482 AC: 73235 AN: 152046 Hom.: 18217 Cov.: 32 AF XY: 0.479 AC XY: 35582 AN XY: 74318

African (AFR) AF: 0.374 AC: 15488 AN: 41456

American (AMR) AF: 0.458 AC: 6998 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2169 AN: 3472

East Asian (EAS) AF: 0.392 AC: 2022 AN: 5164

South Asian (SAS) AF: 0.516 AC: 2493 AN: 4828

European-Finnish (FIN) AF: 0.481 AC: 5082 AN: 10566

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37279 AN: 67980

Other (OTH) AF: 0.521 AC: 1101 AN: 2112

Alfa AF: 0.531 Hom.: 96495

Bravo AF: 0.473

Asia WGS AF: 0.466 AC: 1621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.71
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2718107; hg19: chr7-128838659;